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Trial record 5 of 48 for:    neurology AND University AND San Francisco | Recruiting, Not yet recruiting, Available Studies

Salsalate in Patients Mild to Moderate Alzheimer's Disease (SAL-AD)

This study is currently recruiting participants.
Verified September 2017 by Adam Boxer, University of California, San Francisco
Sponsor:
ClinicalTrials.gov Identifier:
NCT03277573
First Posted: September 11, 2017
Last Update Posted: September 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Adam Boxer, University of California, San Francisco
  Purpose
The purpose of the study is to test the safety and tolerability of twice daily Salsalate in patients with mild to moderate Alzheimer's Disease. Half of the participants will receive Salsalate and half will receive placebo during the 1-year duration of the study.

Condition Intervention Phase
Alzheimer Disease Drug: Salsalate Drug: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized, Double-Blind, Placebo-Controlled
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Double-Blind study. Only investigational pharmacist will be unblinded.
Primary Purpose: Treatment
Official Title: A Phase 1b, 12-Month, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Salsalate in Patients With Mild to Moderate Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Adam Boxer, University of California, San Francisco:

Primary Outcome Measures:
  • Incidence of Treatment-Emergent Adverse Events [ Time Frame: 12 months ]
    Assess adverse events during 12 months administration of Salsalate or Placebo


Secondary Outcome Measures:
  • Changes in Pharmacokinetic properties of Salsalate in Plasma and Cerebrospinal Fluid [ Time Frame: 6; 11.5 months ]
    Measure steady-state plasma and cerebrosinal fluid concentrations of salsalate and its metabolites.

  • Changes in Pharmacodynamic properties of Salsalate in Cerebrospinal Fluid [ Time Frame: 6; 11.5 months ]
    Measure CSF concentrations of total tau, phosphorylated tau, and neurofilament light chain


Other Outcome Measures:
  • Change in brain volume on brain MRI [ Time Frame: 6; 12 months ]
    Measure of global and regional volumes of interest (such as hippocampus)

  • Change in structural and functional connectivity on brain MRI [ Time Frame: 6; 12 months ]
    Connectivity between brain regions measured using diffusion tensor MRI and resting state functional MRI

  • Change in Cerebrospinal Fluid Biomarkers of phosphorylated tau [ Time Frame: 6; 11.5 months ]
    Measure CSF concentrations of phosphorylated tau protein (p-tau) pg/mL

  • Change in Cerebrospinal Fluid Biomarkers of neurofilament light chain [ Time Frame: 6; 11.5 months ]
    Measure CSF concentrations of neurofilament light chain protein (NfL) pg/ml

  • Change in Cerebrospinal Fluid Biomarkers of total tau [ Time Frame: 6; 11.5 months ]
    Measure CSF concentrations of total tau protein (t-tau) pg/mL

  • Change in Cerebrospinal Fluid Biomarkers of beta amyloid 1-42 [ Time Frame: 6; 11.5 months ]
    Measure CSF concentrations of beta amyloid protein (Abeta1-42) pg/mL

  • Change in Alzheimer's Disease Assessment Scale-cognitive scale [ Time Frame: 6;12 months ]
    Measure changes using the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) which evaluates cognitive dysfunctions

  • Change in Mini Mental State Examination [ Time Frame: 6;12 months ]
    Measure changes using the Mini Mental State Exam (MMSE) which evaluates cognitive function.

  • Change in Alzheimer's disease Clinical Activities of Daily Living Scale [ Time Frame: 6;12 months ]
    Measure changes in function, and in particular the degree of disability using the Alzheimer's disease Clinical Activities of Daily Living scale (ADCS-ADL)

  • Change in Clinical Dementia Rating Scale (CDR-SB) [ Time Frame: 6;12 months ]
    Measure change in dementia status using the Clinical Dementia Rating scale (CDR-SB)


Estimated Enrollment: 40
Actual Study Start Date: July 21, 2017
Estimated Study Completion Date: October 21, 2018
Estimated Primary Completion Date: October 21, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Salsalate
Drug: Salsalate 2 tablets twice daily (3,000 mg total daily) by mouth for 12 months
Drug: Salsalate
Salsalate is a non-acetylated dimer of salicylic acid, and is classified as a non-steroidal anti-inflammatory drug (NSAID). Salsalate has been commercially available in the US as a prescription drug for the relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and related rheumatic disorder for decades.
Placebo Comparator: Placebo
Drug: Placebo 2 tablets twice daily by mouth for 12 months
Drug: Placebo
Inactive ingredient

Detailed Description:

This is a Phase 1b, 12-month, randomized, double-blind, placebo-controlled study of the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of salsalate in patients with mild to moderate AD. Approximately 40 subjects will be randomized 1:1 to placebo or active. All study drugs will be administered orally bid [two placebo tablets bid or two 750 mg salsalate tablets bid (for a total daily dose of 3,000 mg)] for 12 months.

This study will test the effects of Salsalate on cerebrospinal fluid (CSF) proteins, brain magnetic resonance imaging (MRI), and cognitive (thinking and memory) tests in subjects with mild to moderate AD. This study uses placebo which looks like the experimental drug but does not have any active drug in it.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   50 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Between 50 and 85 years of age (inclusive);
  2. Meets National Institute on Aging-Alzheimer's Association Workgroups criteria for probable AD dementia (McKhann et al. 2011) (30);
  3. MRI at Screening is consistent with AD (≤ 4 microhemorrhages, and no large strokes or severe white matter disease);
  4. MHIS at Screening is ≤ 4;
  5. MMSE at Screening is between 14 and 30 (inclusive);
  6. FDA-approved AD medications are allowed as long as the dose is stable for 2 months prior to initial Screening visit. Other medications (except those listed under exclusion criteria) are allowed as long as the dose is stable for 30 days prior to initial Screening visit;
  7. Has a reliable study partner who agrees to accompany the subject to visits, and spends at least 5 hours per week with the subject;
  8. Agrees to the lumbar puncture and CSF collection at Screening and after 11.5 months of study drug administration. The lumbar puncture and CSF collection at the end of Month 6 is optional and is not required for eligibility;
  9. Positive amyloid PET scan at Screening. Previous amyloid PET scan positivity or previous AD biomarker (Aβ/tau level) positivity may be used instead of performing an amyloid PET scan at Screening at the Investigator's discretion;
  10. Signed and dated written informed consent obtained from the subject and the subject's caregiver in accordance with local IRB regulations;
  11. Males and all WCBP agree to abstain from sex or use an adequate method of contraception for the duration of the study and for 30 days after the last dose of study drug.

Exclusion Criteria:

  1. Any medical condition other than AD that could account for cognitive deficits (e.g., active seizure disorder, stroke, vascular dementia);
  2. History of negative AD biomarker studies (CSF Aβ/tau levels or amyloid PET), or a negative amyloid PET scan during Screening;
  3. History of significant cardiovascular, hematologic, renal, or hepatic disease (or laboratory evidence thereof);
  4. Systolic blood pressure exceeding 180 mmHg or diastolic blood pressure exceeding 100 mmHg at Screening or Baseline;
  5. History of peptic ulcer disease or GI bleeding;
  6. History of asthma, urticaria, or allergic-type reactions after taking NSAIDs or aspirin;
  7. History of aspirin triad (i.e., aspirin allergy, nasal polyps, and asthma);
  8. History of autoimmune disorders deemed clinically significant by the Investigator;
  9. History of major psychiatric illness or major depression that in the opinion of the Investigator would pose a safety risk or interfere with the appropriate interpretation of study data;
  10. Neutrophil count <1,500/mm3, platelets <100,000/mm3, serum creatinine >1.5 x upper limit of normal (ULN), total bilirubin >1.5 x ULN, alanine aminotransferase (ALT) >3 x ULN, aspartate aminotransferase (AST) >3 x ULN, or INR >1.2 at Screening;
  11. Evidence of any clinically significant findings on Screening or baseline evaluations which, in the opinion of the Investigator would pose a safety risk or interfere with appropriate interpretation of study data;
  12. Current or recent history (within four weeks prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection;
  13. Current clinically significant viral infection. Subjects with chicken pox, influenza, or flu symptoms are not eligible;
  14. Major surgery within four weeks prior to initial Screening visit;
  15. Unable to tolerate MRI scan at Screening;
  16. Any contraindication to or unable to tolerate lumbar puncture at Screening, including use of anti-coagulant medications such as warfarin. Daily administration of 81 mg aspirin will be allowed as long as the dose is stable for 30 days prior to initial Screening visit;
  17. Chronic use of other NSAIDs or salicylates for any reason, except for daily baby aspirin (81 mg);
  18. Chronic use of oral corticosteroids or other immunosuppressants;
  19. Subjects who, in the opinion of the Investigator, are unable or unlikely to comply with the dosing schedule or study evaluations;
  20. Participation in another AD clinical trial within 3 months of initial Screening visit or treatment with another investigational drug within 30 days of initial Screening visit;
  21. Known hypersensitivity to the inactive ingredients in the study drug (placebo or active);
  22. Pregnant or lactating;
  23. Positive pregnancy test at Screening or Baseline (Day 1);
  24. Cancer within 5 years of initial Screening visit, except for non-metastatic skin cancer or prostate cancer without signs of metastasis
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03277573


Contacts
Contact: Mary E Koestler, RN, PhD, CCRC 415-476-0661 mary.koestler@ucsf.edu
Contact: Noelle Ohanesian 415-476-0669 noelle.ohanesian@ucsf.edu

Locations
United States, California
University of California, San Diego Not yet recruiting
San Diego, California, United States, 92093
Contact: Victoria Shokrollah    858-246-1303    vshokrollah@ucsd.edu   
Contact: Jacqueline Flanagan       jdflanagan@ucsd.edu   
Principal Investigator: Shauna Yuan, MD         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94158
Contact: Noelle Ohanesian, BA    415-476-0669    noelle.ohanesian@ucsf.edu   
Contact: Lauren Fisher, BA    415-514-5745    lauren.fisher@ucsf.edu   
Principal Investigator: Adam L. Boxer, M.D., PhD         
Sponsors and Collaborators
Adam Boxer
Investigators
Principal Investigator: Adam Boxer, MD, PhD UCSF Memory and Aging Center
  More Information

Publications:

Responsible Party: Adam Boxer, Director, Alzheimer's Disease and Frontotemporal Dementia Clinical Trials Program, Professor of Neurology, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03277573     History of Changes
Other Study ID Numbers: UC-SAL-AD-001
First Submitted: July 27, 2017
First Posted: September 11, 2017
Last Update Posted: September 11, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Adam Boxer, University of California, San Francisco:
Salsalate

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Salicylsalicylic acid
Sodium Salicylate
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action